Insecticide treated bed nets (ITNs) show great promise as an intervention to reduce malaria transmission in endemic areas of subSaharan Africa, where the toll of malaria is high. When low toxicity pyrethroids are incorporated into the nets, females of the main vector species Anopheles gambiae, An. arabiensis, and An. funestus are either repelled, deterred, or are killed on contact. In this proposal, we focus on the potential for evolution of resistance to synthetic pyrethroids in ITNs to interfere with sustainability of their use. Our study site is in western Kenya, where the only large scale trial in a holoendemic area with perennial transmission was recently completed, and where approximately 120,000 people are under nets. The four specific aims are: (1) Evaluation of the effect of ITN implementation on vector population genetic and community structure and prevalence of resistance using novel molecular genetic approaches and GIS analyses. (2) Quantification of behavioral responses of Anopheles females to insecticide treated net materials in laboratory and field settings. (3) Evaluation of insecticide mosaic ITN formulations and rotation schemes on entomological transmission parameters in field settings. (4) Cohort epidemiologic analyses of the effects of insecticide mosaics and rotations on malariologic outcomes. Our primary hypothesis is that Insecticide mosaics (i.e., simultaneously presented or temporally rotated insecticides in net materials) provide the means of moderating and managing the effects of resistance under operational conditions. We will develop and evaluate resistance management strategies through incorporation of insecticide mosaics of low toxicity but high and variable activity against these vectors. Included will be both Type I and Type II pyrethroids with varying repellence, deterrence, and lethality properties, the hormone mimic pyriproxyphen, the low toxicity carbamate carbosulfan, and the low toxicity organophosphate pirimiphos-methyl. Industry partners Vestergaard-Frandsen and Syngenta are directly involved in these efforts, for formulation and evaluation purposes.